21-acetoxy-17α-hydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione | 18762-17-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 21-acetoxy-17α-hydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione
• 英文别名: 21-acetyloxy-17α-hydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione；21-acetoxy-17α-hydroxy-16β-methyl-4,9(11)-pregnadiene-3,20-dione；17α,21-dihydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione 21-acetate；17α-hydroxy-16β-methyl-21-acetoxypregna-4,9(11)-diene-3-20-dione；21-acetoxy-17-hydroxy-16β-methylpregna-4,9(11)diene-3,20-dione；[2-[(8S,10S,13S,14S,16S,17R)-17-hydroxy-10,13,16-trimethyl-3-oxo-2,6,7,8,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate
• CAS: 18762-17-9
• 化学式: C₂₄H₃₂O₅
• 分子量: 400.515
• InChiKey: SNMKPDYDNGYYEM-NZDAKWCRSA-N

物化性质

• 沸点：
  555.4±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  21-acetoxy-17α-hydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione 生成 21-acetoxy-17α-hydroxy-16β-methyl-6-methylene-4,9(11)-pregnadiene-3,20-dione
  参考文献：
  名称：

  Novel 6, 16-dimethylcorticoids, their preparation and use

  摘要：

  式I的化合物，其中键是单键或双键，X是氢、氟、氯或溴，R.sub.1是甲酰基、烷酰基或含有2-8个碳原子的烷氧基烷基，或苯甲酰基，Y是氯、羟基、甲酰氧基或含有2-8个碳原子的烷酰氧基，或苯甲酰氧基，具有有价值的抗炎性能。

  公开号：

  US04555507A1
• 作为产物：
  描述：

  在 potassium citrate 、 三乙胺 作用下， 反应 24.0h， 以88.26%的产率得到21-acetoxy-17α-hydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione
  参考文献：
  名称：

  甾体药物17位侧链的合成方法

  摘要：

  本发明提供了一种甾体药物17位侧链的合成方法，其特征在于该甾体药物17位侧链的合成以化合物Ⅰ为起始原料，经亲核、酯化、消除、氧化反应等反应合成17位侧链，相较于传统工艺，采用3‑羟基丙腈上氰基，而不使用丙酮腈醇或氰化钠等剧毒物，安全、环保性更高，而且各步反应相对容易实现，收率高，纯度高，生产更加经济、安全，更适合工业生产。

  公开号：

  CN108101950A

文献信息

• A corticoid synthesis from 9α-hydroxyandrost-4-ene-3,17-dione via a steroidal allene
  作者：David R. Andrews、Robert A. Giusto、Anantha R. Sudhakar

  DOI：10.1016/0040-4039(96)00583-7

  日期：1996.5

  An alternative synthesis of 17α, 21-dihydroxy-16β-methylpregna-4,9(11)-diene-3,20-dione, an intermediate to the potent anti-inflammatory corticoid, Betamethasone, is described. The key reactions are the bis epoxidation of a C-17,20 allene and the regiospecific elimination of a 9α-methyl carbonate.

  描述了一种强力消炎皮质类固醇倍他米松的中间体17α，21-二羟基-16β-甲基孕烯-4,9（11）-二烯-3,20-二酮的替代合成方法。关键反应是C-17,20丙二烯的双环氧化和9α-甲基碳酸酯的区域特异性消除。
• A novel route for the preparation of betamethasone from 9α-hydroxyandrost-4-ene-3,17-dione (9αOH-AD) by chemical synthesis and fermentation
  作者：Jie Tang、Xirong Liu、Chunlin Zeng、Hao Meng、Mi Tian、Cancheng Guo

  DOI：10.3184/174751917x14925986241025

  日期：2017.5

  A novel and efficient synthesis of betamethasone has been developed from the readily available 9α-hydroxyandrost-4-ene-3,17-dione (9αOH-AD). The 16α-methyl was introduced stereoselectively with CH3Br and converted to the 16β-methyl, the 17-side chain was installed with 2-chlorovinyl ethyl ether in the place of the toxic KCN/HOAc, and a mild fermentation was employed for the 1,2-dehydrogenation, replacing

  已经从容易获得的 9α-羟基雄甾醇-4-烯-3,17-二酮 (9αOH-AD) 开发了一种新型有效的倍他米松合成方法。16α-甲基与 CH3Br 立体选择性地引入并转化为 16β-甲基，17-侧链安装有 2-氯乙烯乙醚代替有毒的 KCN/HOAc，1, 2-脱氢，取代DDQ氧化。通过对步骤的调整和改进，该路线分11步生产倍他米松，总收率22.9%，显示出其毒性和成本较低的工业应用潜力。
• Anti-inflammatory steroid
  申请人：The Upjohn Company

  公开号：US03980778A1

  公开（公告）日：1976-09-14

  The disclosure covers the preparation of the compound, 6.alpha.,9.alpha.-difluoro-11.beta.,17,21-trihydroxy-16.beta.-methylpregna -1,4-diene-3,20-dione 17.alpha.,21-diacetate, (1) and methods and formulations for its anti-inflammatory use topically, orally and parenterally.

  该披露涵盖了化合物6.alpha.,9.alpha.-二氟-11.beta.,17,21-三羟基-16.beta.-甲基孕酮-1,4-二烯-3,20-二酮17.alpha.,21-二乙酸酯（1）的制备，以及其在局部、口服和静脉注射抗炎用途的方法和配方。
• Steroid intermediates and processes for their preparation
  申请人：Schering Corporation

  公开号：US05502183A1

  公开（公告）日：1996-03-26

  Novel steroids having a 9.alpha.-hydroxy or a 9.alpha.-carbonate substituent can be prepared from 9.alpha.-hydroxyandrostenedione and can be utilized in the synthesis of commercially valuable corticosteroids such as betamethasone. The 9.alpha.-carbonates are prepared by reaction of the corresponding 9.alpha.-hydroxy steroid with a sequence of excess base, trialkylsilyl chloride, alkyl haloformate and alkanol or by using excess base, alkyl haloformate and alkoxide. 9.alpha.-Carbonate-17-keto compounds can be treated with lithium acetylide and a lithium salt to afford the corresponding 17.alpha.-ethynyl-17.beta.-hydroxy-9.alpha.-carbonate. This compound is then esterified with a novel series of reagents to give the 17-ester which can be reduced the corresponding 17-allene. Oxidation of this allene to the bis-epoxide compound, followed by treatment with an alkali metal salt of a carboxylic acid under phase transfer conditions gives the 17.alpha.-hydroxy 21-ester 9.alpha.-carbonate. Elimination of the 9.alpha.-carbonate group affords the a 17.alpha.-hydroxy, 9(11)ene, which in a few subsequent steps can be converted to a variety of commercially important corticosteroids. Novel 9.alpha.-carbonate compounds are prepared in the various reaction steps.

  新型类固醇具有9.alpha.-羟基或9.alpha.-碳酸酯取代基，可以从9.alpha.-羟基雄烯二酮中制备，并可用于合成商业上有价值的皮质类固醇，如倍他米松。9.alpha.-碳酸酯可通过相应的9.alpha.-羟基类固醇与过量碱、三烷基氯硅烷、烷基卤酸酯和烷醇的反应序列，或者通过使用过量碱、烷基卤酸酯和碱性氧化物来制备。9.alpha.-碳酸酯-17-酮化合物可与锂乙炔和锂盐反应，以得到相应的17.alpha.-乙炔基-17.beta.-羟基-9.alpha.-碳酸酯。然后，将这种化合物与新型系列试剂酯化，得到17-酯，可以还原为相应的17-烯基。将这种烯基氧化为双环氧化合物，然后在相转移条件下用羧酸的碱金属盐处理，得到17.alpha.-羟基21-酯9.alpha.-碳酸酯。消除9.alpha.-碳酸酯基团得到17.alpha.-羟基，9(11)烯，经过几个步骤可转化为各种商业重要的皮质类固醇。在各种反应步骤中制备新型9.alpha.-碳酸酯化合物。
• Steroid dehydrogenation
  申请人：THE UPJOHN COMPANY

  公开号：EP0127294A1

  公开（公告）日：1984-12-05

  A process for preparing a 1,2-dehydro-3-keto-steroid, which comprises exposing a 1,2-saturated-3-keto-steroid to a preparation containing steroid-1-dehydrogenase activity in the presence of an added electron carrier and a scavenger for toxic oxygen species.

  一种制备 1,2-脱氢-3-酮-类固醇的工艺，包括将 1,2-饱和-3-酮-类固醇与含有类固醇-1-脱氢酶活性的制剂接触，同时加入电子载体和有毒氧清除剂。